Restenosis is one of the serious complications of vascular interventions. such as balloon angioplasty, laser angioplasty, atherectomy and stenting. It also occurs after bypass grafting using autologous vessels or artificial grafts. Despite the use of drugs which inhibit platelet aggregation, thrombosis, smooth muscle proliferation, and/or immuno-suppresive and anti-cancer agents, restenosis occurs in 10–40% of patients who underwent vascular interventions or grafting. However, there are no clinically available compounds or tools which can completely prevent restenosis (Di Mario C: Heart 84: 471–475, 2000).
It has been generally believed that vascular smooth muscle cells (SMCs) pre-existing in the media migrate into the intima, proliferate excessively and differentiate into collagen fibers with subsequent production of abundant extracellular matrix, resulting in intimal hyperplasia and accordingly in restenosis (Schwartz R S: Am J Cardiol 81: 14E–17E, 1998).
Recently, however, it was demonstrated that bone marrow-derived vascular progenitor cells migrate into the intima from vascular lumen and cause intimal hyperplasia of mechanically injured animal vessels (Orlic D, et al: Proc Natl Acad Sci USA 98: 10344–10349, 2001; Sata M et al: Nature Science 8: 403–409, 2002.). Also, the progenitor cells participate in restenosis at the site of implanted artificial grafts and aortic transplant arteriopathy (Shimizu K: Nature Science 7: 738–741, 2001).